Somatic cell hybridization techniques to produce monoclonal antibodies of defined class, avidity, and specificity were first developed by Kohler, G. and Milstein, C., Nature, 256: 495-497 (1975). Briefly, the technique involves fusing myeloma cells and lymphocytes using a fusogen such as polyethylene glycol. The fused cells or hybridomas are then expanded in a nutrient medium and then selected by incubation in a selective medium such as HAT medium. The cells surviving the incubation are assayed for production of the desired antibody and positive hybrids are sorted and cloned. The monoclonal antibodies produced by the clones may be harvested and purified.
U.S. Pat. No. 4,172,124 uses the above described method to make hybridomas that produce monoclonal antibodies against human tumor cells. The patent specifically describes the preparation of monoclonal antibodies against human melanoma cells and human colorectal carcinoma cells by hybridizing mouse myeloma cells to spleen cells from mice immunized with such tumor cells.
Heterologous anti-idiotype antibodies against human B-cell tumors have been prepared and studied by Levy, R. et al. Monoclonal Antibodies, Plenum Press, Ed by Kennet, et al, 1980, pp 137-153. Brown, S. et al, J. Immun. (1980) 125: 1037-1043 also describe such antibodies. These antibodies were prepared by hybridizing non-Ig secreting human B-leukemia cells to mouse myeloma cells to produce human Ig secreting hybridomas. The human Ig secreted by the fused cells was used as an immunogen to immunize rabbits which produced anti-idiotype antibodies against the surface Ig of the tumor cells. Hough, et al, J. Exp. Med., 1976, 144: 960 also made heterologous anti-idiotype antibodies against human B-cell tumors using Fab.mu. fragments released from tumor cell surfaces by limited papain digestion as an immunogen.